50648-94-7Relevant articles and documents
Chemical Synthesis of Side-Chain-Hydroxylated Vitamin D3 Derivatives and Their Metabolism by CYP27B1
Iwaki, Miho,Mizumoto, Yuka,Nagasawa, Kazuo,Nagata, Akiko,Ohshita, Haruki,Sakaki, Toshiyuki,Sakamoto, Ryota,Yasuda, Kaori
, p. 2896 - 2900 (2021/07/31)
1α,25-Dihydroxyvitamin D3 (abbreviated here as 1,25D3) is a hormonally active form of vitamin D3 (D3), and is produced from D3 by CYP27 A1-mediated hydroxylation at C25, followed by CYP27B1-mediated hydroxylation at C1. Further hydroxylation of 25D3 and 1,25D3 occurs at C23, C24 and C26 to generate corresponding metabolites, except for 1,25R,26D3. Since the capability of CYP27B1 to hydroxylate C1 of side-chain-hydroxylated metabolites other than 23S,25D3 and 24R,25D3 has not been examined, we have here explored the role of CYP27B1 in the C1 hydroxylation of a series of side-chain-hydroxylated D3 derivatives. We found that CYP27B1 hydroxylates the R diastereomers of 24,25D3 and 25,26D3 more effectively than the S diastereomers, but shows almost no activity towards either diastereomer of 23,25D3. This is the first report to show that CYP27B1 metabolizes 25,26D3 to the corresponding 1α-hydroxylated derivative, 1,25,26D3. It will be interesting to examine the physiological relevance of this finding.
Metabolism of substrates incorporated into phospholipid vesicles by mouse 25-hydroxyvitamin D3 1α-hydroxylase (CYP27B1)
Tang, Edith K.Y.,Voo, Kimberley J.Q.,Nguyen, Minh N.,Tuckey, Robert C.
experimental part, p. 171 - 179 (2011/02/23)
CYP27B1 catalyzes the 1α-hydroxylation of 25-hydroxyvitamin D3 to 1α,25-dihydroxyvitamin D3, the hormonally active form of vitamin D3. To further characterize mouse CYP27B1, it was expressed in Escherichia coli, purified and its activity measured on substrates incorporated into phospholipid vesicles, which served as a model of the inner mitochondrial membrane. 25-Hydroxyvitamin D3 and 25-hydroxyvitamin D2 in vesicles underwent 1α-hydroxylation with similar kinetics, the catalytic rate constants (kcat) were 41 and 48mol/min/mol P450, respectively, while Km values were 5.9 and 4.6mmol/mol phospholipid, respectively. CYP27B1 showed inhibition when substrate concentrations in the membrane were greater than 4 times Km, more pronounced with 25-hydroxyvitamin D3 than 25-hydroxyvitamin D2. Higher catalytic efficiency was seen in vesicles prepared from dioleoyl phosphatidylcholine and cardiolipin than for dimyristoyl phosphatidylcholine vesicles. CYP27B1 also catalyzed 1α-hydroxylation of vesicle-associated 24R,25-dihydroxyvitamin D3 and 20-hydroxyvitamin D3, and 25-hydroxylation of 1α-hydroxyvitamin D3 and 1α-hydroxyvitamin D2, but with much lower efficiency than for 25(OH)D3. This study shows that CYP27B1 can hydroxylate 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3 associated with phospholipid membranes with the highest activity yet reported for the enzyme. The expressed enzyme has low activity at higher concentrations of 25-hydroxyvitamin D in membranes, revealing that substrate inhibition may contribute to the regulation of the activity of this enzyme.
Synthesis of active forms of vitamin D. VIII. Synthesis of [24R] and [24S] 1α,24,25 trihydroxyvitamin D3
Ikekawa,Morisaki,Koizumi,et al.
, p. 695 - 697 (2007/10/10)
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